Targeting a brain region called the amygdala with a procedure known as neurofeedback improved sleep quality and reduced depression and anxiety, associated with less chronic pain in the long term in fibromyalgia patients, a study reports.

Volitional neuromodulation, or neurofeedback, measures a person’s brain waves and provides feedback to reorganize or retrain those brain signals. Neurofeedback may be particularly useful in somatic disorders such as chronic pain and insomnia, but its precise effects remain to be determined.

Chronic pain in fibromyalgia has been suggested as a multistep process involving impaired mood regulation and sleep quality, which, in turn, may lead to further neural, physiological, and behavioral changes, as well as increased pain, in a vicious cycle.

The amygdala plays a key role in the regulation of pain, sleep, and emotion. Fibromyalgia patients show altered function of the limbic system, which includes the amygdala, as well as reduced gray matter volume — including cell bodies, their projections, and the sites where neurons communicate, called synapses — within this region.

Because abnormal limbic system function has also been shown in people with sleep deprivation, scientists in Israel hypothesized that neurofeedback targeting limbic activity could be beneficial for fibromyalgia patients.

Functional magnetic resonance imaging (fMRI)-neurofeedback has shown successful modulation of amygdala activity in healthy individuals, as well as in patients with post-traumatic stress disorder, personality disorder, and major depression. Also targeting the limbic system, this approach lessened chronic pain in two studies, but more evidence is needed.

Aiming to overcome the high cost, limitations in equipment availability, and factors that may exclude patients from MRI scans, the team developed an approach combining high anatomical resolution and widespread availability, the first of which is an advantage of fMRI and the latter of electroencephalogram (EEG).

In previous work in healthy participants, neurofeedback using the investigators’ simultaneous EEG/fMRI recording, called the Amygdala-Electrical Fingerprint (Amyg-EFP), led to improved emotion regulation.

The scientists conducted a double-blind, placebo-controlled trial (NCT02146495) in 34 patients with fibromyalgia (31 women, with a mean age of 35.6) intended to train individuals to lower the Amyg-EFP signal, and to assess the effects on chronic pain, sleep, and emotion regulation.

They used self-reported questionnaires of pain, sleep, anxiety, depression and fatigue, and obtained objective measures of sleep quality, particularly rapid eye movement (REM) sleep latency — time from the start of sleeping and the first REM episode — known to be related to amygdala activation.

A total of 10 neurofeedback sessions, twice a week, were conducted for five consecutive weeks. Each session either used an auditory interface (a soft piano tune), an animated scenario interface (virtual characters losing their patience), or both. Within each session, the neurofeedback trials contained two conditions, rest and regulate, with participants instructed to modulate the interface only during the regulate condition.

The 25 patients on Amyg-EFP-neurofeedback were then divided into 13 good (all women) and 12 poor modulators (11 women) based on their success in the neurofeedback training. Follow-up was conducted for up to three years (a mean of 16.2 months) after training completion.

Results showed that patients on Amyg-EFP-neurofeedback, particularly the good modulators, had marked improvements in REM latency and composite sleep score — reflecting sleep latency (time between going to bed and falling asleep), sleep efficiency (the ratio of total time spent asleep to total time spent in bed), and lack of proper deep sleep total (time spent in deep/REM sleep out of the total sleep time), compared with the nine in the placebo group. Self-reported measures were unchanged at the end of the treatment.

Follow-up results revealed a delayed reduction in chronic pain — at least a 40% decrease in the visual analog scale (VAS) score — and improvement in subjective sleep experience in patients in the Amyg-EFP group. A subsequent analysis showed that these follow-up effects on pain were predicted by the post-training improvements in objective sleep assessed through the composite sleep score, and in self-reported depression and anxiety.

“These results suggest that when both objective sleep and affective symptoms were improved initially, pain intensity in the follow-up assessment was improved to the greatest extent,” the scientists wrote.

“This indirect approach to chronic pain management reflects the necessary link between somatic and affective dysregulation that can be successfully targeted using neurofeedback,” they added.

Noting that the findings need to be validated in larger groups of patients, the team also said that “the demonstration that a low-cost mechanism-based EEG-[neurofeedback] treatment can be clinically valuable in Fibromyalgia patients carries significant hope.”